Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues.
Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues.
复制标题
编码朊病毒蛋白前导肽的 cDNA 克隆的分离以及同源基因在各种组织中的表达。
DOI：
10.1073/pnas.83.17.6377
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发表时间：
1986
影响因子：
11.1
通讯作者：
Innis,MA
中科院分区：
文献类型：
--
作者：
Robakis,NK;Sawh,PR;Wolfe,GC;Rubenstein,R;Carp,RI;Innis,MA
我们已经分离出一个仓鼠cDNA克隆，代表朊病毒蛋白（PrP）27-30的整个前体的编码序列。该克隆编码一个254个残基的蛋白质，并含有一个符合读框的ATG密码子，该密码子位于先前报道的密码子上游42个碱基处。预测的氨基酸序列的分析表明，PrP前体蛋白含有一个氨基末端的信号序列，和一个跨膜结构域的羧基末端。信号肽的切割将产生232个氨基酸的成熟蛋白质。在仓鼠、小鼠、绵羊、人和兔基因组中检测到与仓鼠PrP cDNA同源的序列。一个相关的2.5-乙酰胆碱酯酶转录本存在于正常和羊瘙痒病感染的啮齿动物的大脑中。在正常动物的肺和心脏中检测到两种同源转录物，2.5和1.1内切酶。在已知含有高滴度羊瘙痒病的脾基质组织中未检测到PrP mRNA。抗血清提高到27至30 kDa的多肽检测PrP在正常和感染的大脑，但未能检测到这种蛋白质在正常或感染的脾脏。在人类、绵羊和兔子的大脑中检测到了同源基因mRNA，尽管后者对羊瘙痒病感染有抵抗力。我们的数据表明，PrP不是感染因子的必要组成部分。
We have isolated a hamster cDNA clone representing the coding sequences for the entire precursor of prion protein (PrP) 27-30. This clone encodes a protein of 254 residues and contains an in-frame ATG codon 42 bases upstream from the one previously reported. Analysis of the predicted amino acid sequence suggests that the PrP precursor protein contains an amino-terminal signal sequence, and a membrane-spanning domain in the carboxyl terminus. Cleavage of the signal peptide would produce a mature protein of 232 amino acids. Sequences homologous to the hamster PrP cDNA were detected in hamster, mouse, sheep, human, and rabbit genomes. A related 2.5-kilobase transcript was present in the brain of normal and scrapie-infected rodents. Two homologous transcripts, 2.5 and 1.1 kilobases, were detected in the lung and heart of normal animals. No PrP mRNA was detected in spleen stroma, a tissue known to contain high titers of scrapie. Antisera raised to the 27- to 30-kDa polypeptide detected the PrP in both normal and infected brains but failed to detect this protein in either normal or infected spleens. Homologous mRNA species were detected in human, sheep, and rabbit brain, even though the latter is resistant to scrapie infection. Our data suggest that PrP is not a necessary component of the infectious agent.